BR112021014402A2 - Métodos de tratamento de doença com inibidores de magl - Google Patents
Métodos de tratamento de doença com inibidores de magl Download PDFInfo
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- BR112021014402A2 BR112021014402A2 BR112021014402-1A BR112021014402A BR112021014402A2 BR 112021014402 A2 BR112021014402 A2 BR 112021014402A2 BR 112021014402 A BR112021014402 A BR 112021014402A BR 112021014402 A2 BR112021014402 A2 BR 112021014402A2
- Authority
- BR
- Brazil
- Prior art keywords
- formula
- alkyl
- compound
- methods
- treating dyskinesia
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 1105
- 201000010099 disease Diseases 0.000 title abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 13
- 239000003112 inhibitor Substances 0.000 title abstract description 4
- 238000011282 treatment Methods 0.000 title description 10
- 102100029814 Monoglyceride lipase Human genes 0.000 title 1
- 101710116393 Monoglyceride lipase Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 1016
- 208000012661 Dyskinesia Diseases 0.000 claims description 960
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 721
- 229910052736 halogen Inorganic materials 0.000 claims description 374
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 306
- 150000002367 halogens Chemical class 0.000 claims description 258
- 229910052757 nitrogen Inorganic materials 0.000 claims description 213
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 176
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 174
- 150000003839 salts Chemical class 0.000 claims description 131
- 125000005843 halogen group Chemical group 0.000 claims description 129
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 106
- 239000012453 solvate Substances 0.000 claims description 102
- 125000000623 heterocyclic group Chemical group 0.000 claims description 94
- 125000001424 substituent group Chemical group 0.000 claims description 94
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 69
- 125000004043 oxo group Chemical group O=* 0.000 claims description 66
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 61
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 46
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 43
- 229910052760 oxygen Inorganic materials 0.000 claims description 41
- 229910052717 sulfur Inorganic materials 0.000 claims description 38
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 36
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 32
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 32
- 229960004502 levodopa Drugs 0.000 claims description 27
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 19
- 102000005398 Monoacylglycerol Lipase Human genes 0.000 abstract description 11
- 108020002334 Monoacylglycerol lipase Proteins 0.000 abstract description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 383
- 125000001072 heteroaryl group Chemical group 0.000 description 155
- -1 -OH Chemical group 0.000 description 144
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 143
- 235000002639 sodium chloride Nutrition 0.000 description 126
- 125000004093 cyano group Chemical group *C#N 0.000 description 103
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 101
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 70
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 70
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 62
- 125000000217 alkyl group Chemical group 0.000 description 61
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 60
- 125000000753 cycloalkyl group Chemical group 0.000 description 54
- 125000002947 alkylene group Chemical group 0.000 description 48
- 125000003118 aryl group Chemical group 0.000 description 48
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 40
- 125000004432 carbon atom Chemical group C* 0.000 description 40
- 229910052799 carbon Inorganic materials 0.000 description 39
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 35
- 150000003254 radicals Chemical class 0.000 description 28
- 239000002253 acid Substances 0.000 description 24
- 229910052739 hydrogen Inorganic materials 0.000 description 23
- 239000003814 drug Substances 0.000 description 21
- 125000003710 aryl alkyl group Chemical group 0.000 description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
- 229940124597 therapeutic agent Drugs 0.000 description 18
- 125000003709 fluoroalkyl group Chemical group 0.000 description 17
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 17
- 239000000126 substance Substances 0.000 description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 15
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 14
- 239000001257 hydrogen Substances 0.000 description 14
- 125000004452 carbocyclyl group Chemical group 0.000 description 13
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 description 12
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 12
- 125000004122 cyclic group Chemical group 0.000 description 12
- 229910052731 fluorine Inorganic materials 0.000 description 12
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 11
- 125000003342 alkenyl group Chemical group 0.000 description 11
- 125000004450 alkenylene group Chemical group 0.000 description 11
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- 125000005842 heteroatom Chemical group 0.000 description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 10
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 9
- 125000000304 alkynyl group Chemical group 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 229910052705 radium Inorganic materials 0.000 description 9
- 229910052701 rubidium Inorganic materials 0.000 description 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 8
- 244000201986 Cassia tora Species 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- NCAIGTHBQTXTLR-UHFFFAOYSA-N phentermine hydrochloride Chemical compound [Cl-].CC(C)([NH3+])CC1=CC=CC=C1 NCAIGTHBQTXTLR-UHFFFAOYSA-N 0.000 description 8
- 125000003386 piperidinyl group Chemical group 0.000 description 8
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 7
- 229960003805 amantadine Drugs 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 125000005884 carbocyclylalkyl group Chemical group 0.000 description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 7
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 6
- 241000282567 Macaca fascicularis Species 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 description 6
- 125000003107 substituted aryl group Chemical group 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 238000002648 combination therapy Methods 0.000 description 5
- 239000002131 composite material Substances 0.000 description 5
- 125000001841 imino group Chemical group [H]N=* 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- RCRCTBLIHCHWDZ-UHFFFAOYSA-N 2-Arachidonoyl Glycerol Chemical compound CCCCCC=CCC=CCC=CCC=CCCCC(=O)OC(CO)CO RCRCTBLIHCHWDZ-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 230000004064 dysfunction Effects 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 4
- WYZZNMWIWHRXRM-UHFFFAOYSA-N 2,8-diazaspiro[4.5]decane Chemical compound C1NCCC21CCNCC2 WYZZNMWIWHRXRM-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- JVBOTGLQUHBBCV-UHFFFAOYSA-N 8-oxa-2-azaspiro[4.5]decane Chemical compound C1NCCC21CCOCC2 JVBOTGLQUHBBCV-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 208000000269 Hyperkinesis Diseases 0.000 description 3
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 125000004419 alkynylene group Chemical group 0.000 description 3
- 150000005840 aryl radicals Chemical class 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940126086 compound 21 Drugs 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
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- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 3
- 239000011593 sulfur Chemical group 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 125000000464 thioxo group Chemical group S=* 0.000 description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
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- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
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- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- SAHMVBVNTKLMJU-ZDUSSCGKSA-N (2S)-2-[2-[[8-(1,1,1,3,3,3-hexafluoropropan-2-yloxycarbonyl)-1,8-diazaspiro[4.5]decan-1-yl]methyl]-5-(trifluoromethyl)anilino]propanoic acid Chemical compound C[C@H](Nc1cc(ccc1CN1CCCC11CCN(CC1)C(=O)OC(C(F)(F)F)C(F)(F)F)C(F)(F)F)C(O)=O SAHMVBVNTKLMJU-ZDUSSCGKSA-N 0.000 description 1
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- 125000005455 trithianyl group Chemical group 0.000 description 1
- 239000004108 vegetable carbon Substances 0.000 description 1
- 235000012712 vegetable carbon Nutrition 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000019235 yellow 2G Nutrition 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 235000016804 zinc Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
- C07D231/40—Acylated on said nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Psychology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US201962796941P | 2019-01-25 | 2019-01-25 | |
US62/796,941 | 2019-01-25 | ||
PCT/US2020/015083 WO2020154683A1 (fr) | 2019-01-25 | 2020-01-24 | Méthodes de traitement d'une maladie à l'aide d'inhibiteurs de magl |
Publications (1)
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BR112021014402A2 true BR112021014402A2 (pt) | 2021-09-21 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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BR112021014402-1A BR112021014402A2 (pt) | 2019-01-25 | 2020-01-24 | Métodos de tratamento de doença com inibidores de magl |
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Country | Link |
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US (1) | US20220110933A1 (fr) |
EP (1) | EP3914589A4 (fr) |
JP (1) | JP2022523668A (fr) |
KR (1) | KR20210120020A (fr) |
CN (1) | CN113330005A (fr) |
AU (1) | AU2020212596A1 (fr) |
BR (1) | BR112021014402A2 (fr) |
CA (1) | CA3125636A1 (fr) |
CL (1) | CL2021001922A1 (fr) |
IL (1) | IL284791A (fr) |
MA (1) | MA54827A (fr) |
MX (1) | MX2021008865A (fr) |
SG (1) | SG11202108008PA (fr) |
WO (1) | WO2020154683A1 (fr) |
ZA (1) | ZA202104709B (fr) |
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Publication number | Priority date | Publication date | Assignee | Title |
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JOP20200276A1 (ar) | 2018-05-15 | 2020-11-02 | Lundbeck La Jolla Research Center Inc | مثبطات أحادي أسيل جليسرول ليباز (magl) |
CN114761382A (zh) * | 2019-11-15 | 2022-07-15 | H.隆德贝克有限公司 | Magl抑制剂的晶型 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2013049332A1 (fr) * | 2011-09-29 | 2013-04-04 | Infinity Pharmaceuticals, Inc. | Inhibiteurs de monoacylglycérol lipase et procédés de leur utilisation |
PL2800565T3 (pl) * | 2012-01-06 | 2020-09-21 | Lundbeck La Jolla Research Center, Inc. | Związki karbaminianowe i sposoby ich wytwarzania oraz zastosowanie |
JP2018513119A (ja) * | 2015-03-18 | 2018-05-24 | アビデ セラピューティクス,インク. | ピペラジンカルバメート、およびピペラジンカルバメートを製造ならびに使用する方法 |
JOP20190106A1 (ar) * | 2016-11-16 | 2019-05-09 | Lundbeck La Jolla Research Center Inc | مثبطات أحادي أسيل جليسرول ليباز (magl) |
SG11201906427QA (en) * | 2017-01-23 | 2019-08-27 | Pfizer | Heterocyclic spiro compounds as magl inhibitors |
JOP20200276A1 (ar) * | 2018-05-15 | 2020-11-02 | Lundbeck La Jolla Research Center Inc | مثبطات أحادي أسيل جليسرول ليباز (magl) |
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2020
- 2020-01-24 KR KR1020217026417A patent/KR20210120020A/ko unknown
- 2020-01-24 BR BR112021014402-1A patent/BR112021014402A2/pt unknown
- 2020-01-24 MA MA054827A patent/MA54827A/fr unknown
- 2020-01-24 WO PCT/US2020/015083 patent/WO2020154683A1/fr active Application Filing
- 2020-01-24 AU AU2020212596A patent/AU2020212596A1/en not_active Abandoned
- 2020-01-24 MX MX2021008865A patent/MX2021008865A/es unknown
- 2020-01-24 CA CA3125636A patent/CA3125636A1/fr active Pending
- 2020-01-24 CN CN202080010349.7A patent/CN113330005A/zh active Pending
- 2020-01-24 JP JP2021542518A patent/JP2022523668A/ja active Pending
- 2020-01-24 EP EP20745789.6A patent/EP3914589A4/fr not_active Withdrawn
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SG11202108008PA (en) | 2021-08-30 |
WO2020154683A1 (fr) | 2020-07-30 |
ZA202104709B (en) | 2023-01-25 |
AU2020212596A1 (en) | 2021-08-19 |
US20220110933A1 (en) | 2022-04-14 |
MA54827A (fr) | 2022-05-04 |
EP3914589A4 (fr) | 2022-11-30 |
JP2022523668A (ja) | 2022-04-26 |
IL284791A (en) | 2021-08-31 |
CN113330005A (zh) | 2021-08-31 |
KR20210120020A (ko) | 2021-10-06 |
EP3914589A1 (fr) | 2021-12-01 |
MX2021008865A (es) | 2021-10-26 |
CA3125636A1 (fr) | 2020-07-30 |
CL2021001922A1 (es) | 2022-04-22 |
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